Altered plasma clot properties increase the risk of recurrent deep vein thrombosis: a cohort study

It has been demonstrated that fibrin clots generated from plasma samples obtained from patients with prior thromboembolic events are denser and less susceptible to lysis. Such a prothrombotic fibrin clot phenotype has been suggested as a new risk factor for venous thromboembolism, but its prognostic value is unclear. To assess whether abnormal clot properties can predict recurrent deep vein thrombosis (DVT), we studied 320 consecutive patients aged 18 to 70 years following the first-ever DVT. Plasma clot properties were evaluated after 3 months of anticoagulant treatment since the index event. A mean duration of anticoagulation was 10 months (range, 4-20). Recurrent DVT was observed in 77 patients (25%; 6.6%/year) during a median follow-up of 44 months. Recurrences of DVT were associated with faster formation (-9% lag phase) of denser fibrin networks (-12% fibrin clot permeability [K_s]) and 4% higher maximum absorbance of plasma clots that displayed impaired fibrinolytic degradation (+25% prolonged clot lysis time [CLT]) and a 5% slower rate of increase in D-dimer levels during clot degradation (D-D_rate; all P < .05). Proximal DVT alone, higher C-reactive protein, D-dimer, peak thrombin, lower K_s, shorter lag phase, decreased D-D_rate, and prolonged CLT were independent predictors of recurrences (all P < .05). Individuals characterized by low K_s (≤7.3 × 10^-9 cm²) and prolonged CLT (>96 min) were at the highest risk of recurrent DVT (odds ratio, 15.8; 95% confidence interval, 7.5-33.5). Kaplan-Meier curves showed that reduced K_s and prolonged CLT predicted recurrent DVT. We demonstrate that unfavorably altered clot properties may predict recurrent DVT after anticoagulation withdrawal.